The ultimate goal of these studies is to contribute to the understanding of how chemical carcinogens interact with co-carcinogens to yield enhanced cell transformation in vivo and how the effect of these interactions may be reversed or prevented. The specific aim of this project is to evaluate at the molecular and cellular levels the effect of chemical co-carcinogens on the repair of DNA damage induced by various chemical carcinogens. These studies will permit an evaluation of the ability of co-carcinogens to inhibit the repair of the genetic damage induced by a selected number of chemical and physical carcinogenic agents. Concurrently, it will be determined whether modification of DNA repair results in a corresponding change in the frequency of transformation induced by biological, chemical or physical oncogenic agents. A determination of the amount of unrepaired DNA damage of specific physical chemical forms required to produce an oncogenic event will be determined. These comparisons are vital to the working hypothesis that the underlying events leading to malignant transformation involve unrepaired alterations in cellular DNA. For example, it is known that repair of UV-induced pyrimidine dimers is inversely proportional to the frequency of transformation within the teleost Poecilia formosa. BIBLIOGRAPHIC REFERENCES: Lewis, N.J. Hart, R.W., Gibson, R.E. and Ahmed, F.E. (1977) Approaches to the Rational Design and Evaluation of Environmentally Safe Pesticides. In: A Rational Evaluation of Pesticidal vs. Mutagenic/Carcinogenic Action (Ed. R.W. Hart and H.F. Kraybill) In Press. Chang, C.C., Philipps, C., Trosko, J.E. and Hart, R.W. (1977) Mutagenic and Epigenetic Influences of Caffeine on the Frequencies of UV-Induced Ouabain-Resistant Chinese Hamster Cells. In Press. Cancer Research.